EP1286913A2 - Microfluidic concentration gradient loop - Google Patents

Microfluidic concentration gradient loop

Info

Publication number
EP1286913A2
EP1286913A2 EP01939284A EP01939284A EP1286913A2 EP 1286913 A2 EP1286913 A2 EP 1286913A2 EP 01939284 A EP01939284 A EP 01939284A EP 01939284 A EP01939284 A EP 01939284A EP 1286913 A2 EP1286913 A2 EP 1286913A2
Authority
EP
European Patent Office
Prior art keywords
channel
fluid
inlet
solution
diffusible
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01939284A
Other languages
German (de)
English (en)
French (fr)
Inventor
C. Frederick Battrell
Ronald L. Bardell
Gerald L. Klein
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Micronics Inc
Original Assignee
Micronics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Micronics Inc filed Critical Micronics Inc
Publication of EP1286913A2 publication Critical patent/EP1286913A2/en
Withdrawn legal-status Critical Current

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    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
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    • B01D—SEPARATION
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    • B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
    • B01F33/3011—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
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Definitions

  • This invention relates generally to microfluidic devices for performing analytic testing, and, in particular, to a device and method for generating a stable concentration gradient in a microfluidic channel by varying the flow rate of the solutions flowing within the channel.
  • Microfluidic devices have recently become popular for performing analytic testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively means produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information for the medical field.
  • U.S. Patent No. 5,716,852 teaches a method for analyzing the presence and concentration of small particles in a flow cell using diffusion principles.
  • This patent discloses a channel cell system for detecting the presence of analyte particles in a sample stream using a laminar flow channel having at least two inlet means which provide an indicator stream and a sample stream, where the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and length sufficient to allow diffusion of particles of the analyte into the indicator stream to form a detection area, and having an outlet out of the channel to form a single mixed stream.
  • This device which is known at a T-Sensor, may contain an external detecting means for detecting changes in the indicator stream.
  • This detecting means may be provided by any means known in the art, including optical means such as optical spectroscopy, or absorption spectroscopy of fluorescence.
  • U.S. Patent No. 5,932,100 which patent is also incorporated herein by reference, teaches another method for analyzing particles within microfluidic channels using diffusion principles.
  • a mixture of particles suspended in a sample stream enters an extraction channel from one upper arm of a structure, which comprises microchannels in the shape of an "H".
  • An extraction stream (a dilution stream) enters from the lower arm on the same side of the extraction channel and due to the size of the microfluidic extraction channel, the flow is laminar and the streams do not mix.
  • the sample stream exits as a by-product stream at the upper arm at the end of the extraction channel, while the extraction stream exits as a product stream at the lower arm.
  • particles having a greater diffusion coefficient small particles such as albumin, sugars, and small ions
  • the larger particles blood cells
  • Particles in the exiting extraction stream (now called the product stream) may be analyzed without interference from the larger particles.
  • This microfluidic structure commonly known as an "H-Filter,” can be used for extracting desired particles from a sample stream containing those particles.
  • microfluidic devices use diffusion principles to perform many differential analyses within flowing microchannels. However, it is often helpful to perform a real time analysis on a flowing suspension of substances to determine a reaction of certain compounds across a detection zone.
  • An example of this type of device is described in U.S. Patent No. 6,096,509, which issued on August 1 , 2000.
  • This patent describes an apparatus and method for real time measurement of a cellular response of a test compound or series of test compounds on a flowing suspension of cells. A homogeneous suspension of each member of a series of cell types is combined with a concentration of a test compound which is directed through a detection zone to measure in real time the cellular response as the cells in the test mixture flow through the detection zone.
  • FIG. 1 is an illustration of the fluid flow through the microfluidic flow channel of a T-Sensor
  • FIG. 2 is a cross-sectional view of a section of the flow channel used in the present invention
  • FIG. 3 is a top view of a section of the flow channel of the present invention showing diffusion across the channel
  • FIG. 4 is a view of the channel shown in FIG. 3 after some time has elapsed;
  • FIG. 5 is a three-dimensional graph showing diffusion of material in the longitudinal channel direction after one hour
  • FIG. 6 is a three-dimensional graph showing diffusion of material in the longitudinal channel direction after one month
  • FIG. 7 is a representation of an integrated microfluidic circuit using the principles of the present invention.
  • FIG. 8 is a representation of a device for processing parallel microfluidic channels using the principles of the present invention.
  • FIG. 9 is a view of a section of a channel showing a concentration gradient created by a change in the rate of flow of a solution into the channel.
  • FIG. 10 is a view of a section of channel, similar to FIG. 9, showing a concentration gradient created by a periodic change of the rate of flow a solution into the channel.
  • T-Sensor 10 consists of a sample stream inlet port 12, a sample stream channel 14, an indicator stream port 16, and an indicator stream channel 18.
  • Sample stream channel 14 meets indicator stream channel 18 at T-joint 20 at the beginning of flow channel 22.
  • the flow rates from ports 12 and 16 are constant; both streams 24 and 26 flow at the same rate within its channel without changing.
  • the only mixing that occurs within channel 22 is due to diffusion across the laminar boundary between streams 24 and 26 by smaller particles from sample stream 24. If diffusion within T-Sensor 10 has reached equilibrium, and the flow rate from port 12 is constant and the flow rate from port 16 is constant, channel 22 will then contain a uniform solution, and there is no change in concentration along the length of channel 22.
  • a first solution 50 containing a given concentration of soluble compounds is introduced into a microfluidic channel 52 containing layers 52a-d.
  • solution 50 is injected into channel 52, between layers 52b and 52c.
  • a diluting solution 54 is also introduced into channel 52.
  • Solution 54 is introduced in two sections in the present embodiment, between layers 52a and 52b, and also between layers 52c and 52d. As solution 54 contacts solution 50 on both sides of the stream, solution 50 containing the soluble compounds forms a thin ribbon 60, which is uniformly distributed across the width of channel 52.
  • FIGS. 3 and 4 show the diffusion characteristics of the present embodiment across channel 52.
  • FIG. 3 there is shown a top view of channel 52 showing the diffusion across channel 52 at time X, where the combined solutions are flowing within channel 52 in the direction indicated by arrow A. Particles from solution 50 have begun to diffuse towards walls 62 and 64 of channel 52, forming a pair of regions 66 on either side of solution 50, and a second pair of regions 68 near walls 62 and 64 of channel 52.
  • FIG. 4 which shows channel 52 at time Xj+ ⁇ , shows a uniform solution 70 across channel 52 with the solution flowing in the direction of arrow A, indicating that rapid diffusion has taken place within in a few seconds across the width direction.
  • concentration gradient along the length of the main channel in a microfluidic device. This concentration can be used to efficiently measure the effect on concentration on biological or chemical materials.
  • the creation of a stable concentration gradient is initiated by a change in the flow rate in either the solution containing the soluble compounds or the diluting solution, or both. By changing the ratio of the flow rates of these solutions, the concentration of the soluble compound within the channel can be varied as a function of the length of the channel.
  • FIG. 9 Examples of a concentration gradient within a channel can be seen in FIG. 9.
  • FIG. 9 there is seen microfluidic channel 52 from FIG. 2 at a location spaced downstream, in which the ratio of the flow rates of solutions 50 and 54 is not constant. It can be seen that a concentration gradient has been generated at 80 within channel 52. Thus, while diffusion in
  • FIG. 5 depicts a graph showing the diffusion of material, 500MW, along the channel length of 100mm.
  • the concentration has essentially stabilized over a one-hour time period, showing that the concentration gradient is very stable in the longitudinal direction of channel 52.
  • FIG. 6 depicts the concentration along the length of the 100mm channel over the course of one month (720 hours). It can be seen in this graph that there is very little change over this long time period, proving that the concentration gradient of the present invention is very stable.
  • FIG. 10 shows an example of the channel of FIG. 9 in which the ratio of the flow rates between the solutions.
  • microfluidic channel 52 at a location spaced downstream from the location shown in FIG. 2 when the ratio between the flow rates of the two input solutions is varying periodically, such as sinusoidally.
  • the concentration gradient as shown at 90 in channel 52 varies sinusoidally.
  • FIG. 7 An integrated microfluidic circuit for analyzing samples using a stable concentration gradient is shown in FIG. 7.
  • a circuit generally designated as 100, based on the principles of the present invention.
  • a solution 102 containing soluble compounds is injected into a main channel 104 into a layer of a diluting solution 106, as shown in FIG. 2.
  • the flow rates of either solution 106 and/or solution 102 are varied in order to establish a concentration gradient, which can be seen at 110 in channel 104.
  • a biological material 112 is injected into channel 104 into the concentration gradient.
  • Material 112 may consist of cells or proteins, or it may consist of reactive beads or other chemical material. Material 112 flows within channel 104 and can interact with the concentration gradient, where it may be detected at a first measurement zone 114 or at a second measurement zone 116, which could preferably detect a difference between the measurements at zone 114.
  • circuit 100 shown in FIG. 7 can be applied to a parallel processing system of concentration gradient microchannels which could be used as a drug discovery system.
  • a system generally designated at 130, which contains a plurality of parallel microchannels 132 in which soluble compounds are injected into diluting solution streams 134 all in parallel.
  • a biological or chemical material 136 is injected into each channel, and a pair of sensors 140 monitor the binding or inhibition of binding within an interaction zone 142 to determine the effect on the particular cell or proteins contained within channels 132.
  • This particular embodiment is easily adaptable to drug discovery systems which use a microliter format (8x10), and can be manufactured on a single chip.

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111132765A (zh) * 2017-09-19 2020-05-08 高保真生物技术有限公司 微流体系统中的颗粒分选

Families Citing this family (212)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6601613B2 (en) 1998-10-13 2003-08-05 Biomicro Systems, Inc. Fluid circuit components based upon passive fluid dynamics
US6637463B1 (en) 1998-10-13 2003-10-28 Biomicro Systems, Inc. Multi-channel microfluidic system design with balanced fluid flow distribution
US6591852B1 (en) 1998-10-13 2003-07-15 Biomicro Systems, Inc. Fluid circuit components based upon passive fluid dynamics
USRE40407E1 (en) 1999-05-24 2008-07-01 Vortex Flow, Inc. Method and apparatus for mixing fluids
US6890093B2 (en) 2000-08-07 2005-05-10 Nanostream, Inc. Multi-stream microfludic mixers
EP1309404A2 (en) * 2000-08-07 2003-05-14 Nanostream, Inc. Fluidic mixer in microfluidic system
WO2002074438A2 (en) * 2001-03-19 2002-09-26 Gyros Ab Structural units that define fluidic functions
US7429354B2 (en) 2001-03-19 2008-09-30 Gyros Patent Ab Structural units that define fluidic functions
US20020159920A1 (en) * 2001-04-03 2002-10-31 Weigl Bernhard H. Multiple redundant microfluidic structures cross reference to related applications
WO2002083952A1 (en) * 2001-04-12 2002-10-24 Caliper Technologies Corp. Systems and methods for high throughput genetic analysis
SE0104077D0 (sv) * 2001-10-21 2001-12-05 Gyros Ab A method and instrumentation for micro dispensation of droplets
US6919058B2 (en) 2001-08-28 2005-07-19 Gyros Ab Retaining microfluidic microcavity and other microfluidic structures
GB0123114D0 (en) * 2001-09-26 2001-11-14 Accentus Plc Protein production
US6877892B2 (en) * 2002-01-11 2005-04-12 Nanostream, Inc. Multi-stream microfluidic aperture mixers
US6958119B2 (en) * 2002-02-26 2005-10-25 Agilent Technologies, Inc. Mobile phase gradient generation microfluidic device
US7223371B2 (en) * 2002-03-14 2007-05-29 Micronics, Inc. Microfluidic channel network device
ATE479899T1 (de) * 2002-05-09 2010-09-15 Univ Chicago Einrichtugn und verfahren für druckgesteuerten plug-transport und reaktion
US7901939B2 (en) 2002-05-09 2011-03-08 University Of Chicago Method for performing crystallization and reactions in pressure-driven fluid plugs
US7150834B2 (en) * 2003-07-31 2006-12-19 Arryx, Inc. Multiple laminar flow-based rate zonal or isopycnic separation with holographic optical trapping of blood cells and other static components
US20070166725A1 (en) * 2006-01-18 2007-07-19 The Regents Of The University Of California Multiplexed diagnostic platform for point-of care pathogen detection
US20040038385A1 (en) * 2002-08-26 2004-02-26 Langlois Richard G. System for autonomous monitoring of bioagents
US20040042930A1 (en) * 2002-08-30 2004-03-04 Clemens Charles E. Reaction chamber with capillary lock for fluid positioning and retention
GB0229967D0 (en) 2002-09-18 2003-01-29 Accentus Plc Protein production
US6939450B2 (en) * 2002-10-08 2005-09-06 Abbott Laboratories Device having a flow channel
US20050048669A1 (en) * 2003-08-26 2005-03-03 Nanostream, Inc. Gasketless microfluidic device interface
US6936167B2 (en) * 2002-10-31 2005-08-30 Nanostream, Inc. System and method for performing multiple parallel chromatographic separations
GB0229348D0 (en) * 2002-12-17 2003-01-22 Glaxo Group Ltd A mixing apparatus and method
US7041481B2 (en) 2003-03-14 2006-05-09 The Regents Of The University Of California Chemical amplification based on fluid partitioning
GB0307428D0 (en) 2003-03-31 2003-05-07 Medical Res Council Compartmentalised combinatorial chemistry
GB0307403D0 (en) 2003-03-31 2003-05-07 Medical Res Council Selection by compartmentalised screening
US20060078893A1 (en) 2004-10-12 2006-04-13 Medical Research Council Compartmentalised combinatorial chemistry by microfluidic control
JP2004305009A (ja) * 2003-04-02 2004-11-04 Hitachi Ltd 核酸増幅装置及び核酸増幅方法
US6916113B2 (en) * 2003-05-16 2005-07-12 Agilent Technologies, Inc. Devices and methods for fluid mixing
US7648835B2 (en) * 2003-06-06 2010-01-19 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US7344681B1 (en) * 2003-06-06 2008-03-18 Sandia Corporation Planar micromixer
CN1812839A (zh) * 2003-06-06 2006-08-02 精密公司 在微流体装置上的加热、冷却和热循环的系统与方法
US7160025B2 (en) 2003-06-11 2007-01-09 Agency For Science, Technology And Research Micromixer apparatus and methods of using same
GB0315438D0 (en) * 2003-07-02 2003-08-06 Univ Manchester Analysis of mixed cell populations
US7028536B2 (en) * 2004-06-29 2006-04-18 Nanostream, Inc. Sealing interface for microfluidic device
US9597644B2 (en) 2003-09-05 2017-03-21 Stokes Bio Limited Methods for culturing and analyzing cells
EP1663497B2 (en) 2003-09-05 2020-03-25 Stokes Bio Limited A microfluidic analysis system
US7896865B2 (en) * 2003-09-30 2011-03-01 Codman & Shurtleff, Inc. Two-compartment reduced volume infusion pump
US7776272B2 (en) * 2003-10-03 2010-08-17 Gyros Patent Ab Liquid router
EP1525919A1 (en) * 2003-10-23 2005-04-27 F. Hoffmann-La Roche Ag Flow triggering device
EP1525916A1 (en) * 2003-10-23 2005-04-27 F. Hoffmann-La Roche Ag Flow triggering device
JP2005233802A (ja) * 2004-02-20 2005-09-02 Yokogawa Electric Corp 物理量計測装置およびその装置を用いて行う物理量校正方法
US20050221339A1 (en) 2004-03-31 2005-10-06 Medical Research Council Harvard University Compartmentalised screening by microfluidic control
US7665303B2 (en) 2004-03-31 2010-02-23 Lifescan Scotland, Ltd. Method of segregating a bolus of fluid using a pneumatic actuator in a fluid handling circuit
EP1598429A1 (en) * 2004-05-19 2005-11-23 Amplion Ltd. Detection of amplicon contamination during PCR exhibiting two different annealing temperatures
US7968287B2 (en) 2004-10-08 2011-06-28 Medical Research Council Harvard University In vitro evolution in microfluidic systems
EP1652911A1 (en) * 2004-10-26 2006-05-03 Konica Minolta Medical & Graphic, Inc. Micro-reactor for biological substance inspection and biological substance inspection device
WO2006061026A2 (en) * 2004-12-09 2006-06-15 Inverness Medical Switzerland Gmbh A micro fluidic device and methods for producing a micro fluidic device
GB2421202B (en) * 2004-12-15 2009-12-09 Syrris Ltd Modular microfluidic system
EP1843849A2 (en) * 2005-01-12 2007-10-17 Inverness Medical Switzerland GmbH A method of producing a microfluidic device and microfluidic devices
US7565808B2 (en) * 2005-01-13 2009-07-28 Greencentaire, Llc Refrigerator
EP1874469A4 (en) * 2005-04-14 2014-02-26 Gyros Patent Ab MICROFLUID DEVICE WITH FINGER VALVES
KR100695151B1 (ko) * 2005-05-18 2007-03-14 삼성전자주식회사 교차 채널을 이용한 유체 혼합 장치
CA2610875A1 (en) * 2005-06-06 2006-12-14 Decision Biomarkers, Inc. Assays based on liquid flow over arrays
US20070042406A1 (en) * 2005-07-18 2007-02-22 U.S. Genomics, Inc. Diffusion mediated clean-up of a target carrier fluid
WO2007021819A2 (en) * 2005-08-11 2007-02-22 Eksigent Technologies, Llc Biochemical assay methods
US20090145201A1 (en) * 2005-08-11 2009-06-11 Eksigent Technologies, Llc Methods and apparatuses for reducing effects of molecule adsorption within microfluidic channels
US20070047388A1 (en) * 2005-08-25 2007-03-01 Rockwell Scientific Licensing, Llc Fluidic mixing structure, method for fabricating same, and mixing method
EP1924855A1 (en) * 2005-08-30 2008-05-28 Bayer Healthcare, LLC A test sensor with a fluid chamber opening
US20100137163A1 (en) 2006-01-11 2010-06-03 Link Darren R Microfluidic Devices and Methods of Use in The Formation and Control of Nanoreactors
US9255015B2 (en) 2006-01-17 2016-02-09 Gerald H. Pollack Method and apparatus for collecting fractions of mixtures, suspensions, and solutions of non-polar liquids
US8263360B2 (en) * 2006-01-30 2012-09-11 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Hydrophilic IR transparent membrane, spectroscopic sample holder comprising same and method of using same
CN101410049A (zh) * 2006-01-31 2009-04-15 芝加哥大学 用于检验凝血的方法和设备
EP1981624B1 (en) 2006-02-07 2011-09-07 Stokes Bio Limited A liquid bridge system and method
US20100304446A1 (en) * 2006-02-07 2010-12-02 Stokes Bio Limited Devices, systems, and methods for amplifying nucleic acids
WO2007091230A1 (en) * 2006-02-07 2007-08-16 Stokes Bio Limited A microfluidic analysis system
AU2007225038B2 (en) 2006-03-15 2013-08-29 Perkinelmer Health Sciences, Inc. Integrated nucleic acid assays
US9074242B2 (en) 2010-02-12 2015-07-07 Raindance Technologies, Inc. Digital analyte analysis
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
EP2481815B1 (en) 2006-05-11 2016-01-27 Raindance Technologies, Inc. Microfluidic devices
WO2008021123A1 (en) 2006-08-07 2008-02-21 President And Fellows Of Harvard College Fluorocarbon emulsion stabilizing surfactants
NL1032816C2 (nl) * 2006-11-06 2008-05-08 Micronit Microfluidics Bv Micromengkamer, micromenger omvattende meerdere van dergelijke micromengkamers, werkwijzen voor het vervaardigen daarvan, en werkwijzen voor mengen.
WO2008061129A2 (en) 2006-11-14 2008-05-22 University Of Utah Research Foundation Methods and compositions related to continuous flow thermal gradient pcr
US20100078077A1 (en) * 2006-12-19 2010-04-01 Ismagilov Rustem F Spacers for Microfluidic Channels
WO2008083687A1 (en) * 2007-01-10 2008-07-17 Scandinavian Micro Biodevices Aps A microfluidic device and a microfluidic system and a method of performing a test
US8772046B2 (en) 2007-02-06 2014-07-08 Brandeis University Manipulation of fluids and reactions in microfluidic systems
WO2008130623A1 (en) 2007-04-19 2008-10-30 Brandeis University Manipulation of fluids, fluid components and reactions in microfluidic systems
DE102007020444A1 (de) * 2007-04-27 2008-11-06 Bayer Materialscience Ag Verfahren zur Oxidation eines Chlorwasserstoffenthaltenden Gasgemisches
US7726135B2 (en) 2007-06-06 2010-06-01 Greencentaire, Llc Energy transfer apparatus and methods
US20100227767A1 (en) * 2007-07-26 2010-09-09 Boedicker James Q Stochastic confinement to detect, manipulate, and utilize molecules and organisms
US8043814B2 (en) 2007-07-31 2011-10-25 Eric Guilbeau Thermoelectric method of sequencing nucleic acids
WO2009018473A1 (en) * 2007-07-31 2009-02-05 Micronics, Inc. Sanitary swab collection system, microfluidic assay device, and methods for diagnostic assays
JP5523327B2 (ja) 2007-10-12 2014-06-18 レオニックス，インコーポレイテッド 統合型マイクロ流体デバイスおよび方法
EP2274612B1 (en) * 2008-04-02 2016-10-26 Abbott Point Of Care, Inc. Virtual separation of bound and free label in a ligand assay for performing immunoassays of biological fluids, including whole blood
US8622987B2 (en) * 2008-06-04 2014-01-07 The University Of Chicago Chemistrode, a plug-based microfluidic device and method for stimulation and sampling with high temporal, spatial, and chemical resolution
EP2315629B1 (en) 2008-07-18 2021-12-15 Bio-Rad Laboratories, Inc. Droplet libraries
US12038438B2 (en) 2008-07-18 2024-07-16 Bio-Rad Laboratories, Inc. Enzyme quantification
AT507376B1 (de) 2008-08-29 2013-09-15 Anagnostics Bioanalysis Gmbh Vorrichtung zum temperieren eines rotationssymetrischen behältnisses
EP2337981A1 (en) * 2008-09-17 2011-06-29 Koninklijke Philips Electronics N.V. Microfluidic device
US8709762B2 (en) 2010-03-02 2014-04-29 Bio-Rad Laboratories, Inc. System for hot-start amplification via a multiple emulsion
US11130128B2 (en) 2008-09-23 2021-09-28 Bio-Rad Laboratories, Inc. Detection method for a target nucleic acid
US8633015B2 (en) 2008-09-23 2014-01-21 Bio-Rad Laboratories, Inc. Flow-based thermocycling system with thermoelectric cooler
US9764322B2 (en) 2008-09-23 2017-09-19 Bio-Rad Laboratories, Inc. System for generating droplets with pressure monitoring
US10512910B2 (en) 2008-09-23 2019-12-24 Bio-Rad Laboratories, Inc. Droplet-based analysis method
US9492797B2 (en) 2008-09-23 2016-11-15 Bio-Rad Laboratories, Inc. System for detection of spaced droplets
US9156010B2 (en) 2008-09-23 2015-10-13 Bio-Rad Laboratories, Inc. Droplet-based assay system
US8951939B2 (en) 2011-07-12 2015-02-10 Bio-Rad Laboratories, Inc. Digital assays with multiplexed detection of two or more targets in the same optical channel
WO2011120024A1 (en) 2010-03-25 2011-09-29 Quantalife, Inc. Droplet generation for droplet-based assays
US9417190B2 (en) 2008-09-23 2016-08-16 Bio-Rad Laboratories, Inc. Calibrations and controls for droplet-based assays
US12090480B2 (en) 2008-09-23 2024-09-17 Bio-Rad Laboratories, Inc. Partition-based method of analysis
US9132394B2 (en) 2008-09-23 2015-09-15 Bio-Rad Laboratories, Inc. System for detection of spaced droplets
JP2010082491A (ja) * 2008-09-29 2010-04-15 Fujifilm Corp マイクロデバイス及び液体混合方法
KR101180277B1 (ko) * 2008-12-23 2012-09-07 한국전자통신연구원 미세 유체 제어 장치 및 그의 조립 방법
EP3415235A1 (en) 2009-03-23 2018-12-19 Raindance Technologies Inc. Manipulation of microfluidic droplets
US9464319B2 (en) 2009-03-24 2016-10-11 California Institute Of Technology Multivolume devices, kits and related methods for quantification of nucleic acids and other analytes
US9447461B2 (en) 2009-03-24 2016-09-20 California Institute Of Technology Analysis devices, kits, and related methods for digital quantification of nucleic acids and other analytes
CN104722342B (zh) 2009-03-24 2017-01-11 芝加哥大学 滑动式芯片装置和方法
US10196700B2 (en) 2009-03-24 2019-02-05 University Of Chicago Multivolume devices, kits and related methods for quantification and detection of nucleic acids and other analytes
WO2010141131A1 (en) 2009-06-04 2010-12-09 Lockheed Martin Corporation Multiple-sample microfluidic chip for dna analysis
CA2767056C (en) 2009-09-02 2018-12-04 Bio-Rad Laboratories, Inc. System for mixing fluids by coalescence of multiple emulsions
WO2011042564A1 (en) 2009-10-09 2011-04-14 Universite De Strasbourg Labelled silica-based nanomaterial with enhanced properties and uses thereof
WO2011059559A1 (en) * 2009-11-16 2011-05-19 Sunpower Corporation Water-resistant apparatuses for photovoltaic modules
US10837883B2 (en) 2009-12-23 2020-11-17 Bio-Rad Laboratories, Inc. Microfluidic systems and methods for reducing the exchange of molecules between droplets
US20110165037A1 (en) * 2010-01-07 2011-07-07 Ismagilov Rustem F Interfaces that eliminate non-specific adsorption, and introduce specific interactions
WO2011088247A1 (en) * 2010-01-13 2011-07-21 Nomadics, Inc. In situ-dilution method and system for measuring molecular and chemical interactions
KR101851117B1 (ko) 2010-01-29 2018-04-23 마이크로닉스 인코포레이티드. 샘플-투-앤서 마이크로유체 카트리지
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US10351905B2 (en) 2010-02-12 2019-07-16 Bio-Rad Laboratories, Inc. Digital analyte analysis
US8399198B2 (en) 2010-03-02 2013-03-19 Bio-Rad Laboratories, Inc. Assays with droplets transformed into capsules
CA2767113A1 (en) 2010-03-25 2011-09-29 Bio-Rad Laboratories, Inc. Detection system for droplet-based assays
JP6155419B2 (ja) 2010-03-25 2017-07-05 バイオ−ラッド・ラボラトリーズ・インコーポレーテッド 検出用の液滴輸送システム
WO2011142813A1 (en) * 2010-05-12 2011-11-17 Cellectis Sa Dynamic mixing and electroporation chamber and system
CN102947011B (zh) * 2010-06-15 2015-01-28 3M创新有限公司 带有多个分配针的分配歧管
US20110312841A1 (en) * 2010-06-17 2011-12-22 Geneasys Pty Ltd Fabrication system for lab-on-a-chip (loc) devices with differing application specific functionality
EP3447155A1 (en) 2010-09-30 2019-02-27 Raindance Technologies, Inc. Sandwich assays in droplets
GB2497501A (en) 2010-10-15 2013-06-12 Lockheed Corp Micro fluidic optic design
EP3574990B1 (en) 2010-11-01 2022-04-06 Bio-Rad Laboratories, Inc. System for forming emulsions
US20130005042A1 (en) * 2010-12-30 2013-01-03 Bio-Rad Laboratories, Inc. Hybrid single molecule imaging sorter
EP3412778A1 (en) 2011-02-11 2018-12-12 Raindance Technologies, Inc. Methods for forming mixed droplets
US9150852B2 (en) 2011-02-18 2015-10-06 Raindance Technologies, Inc. Compositions and methods for molecular labeling
CN103534360A (zh) 2011-03-18 2014-01-22 伯乐生命医学产品有限公司 借助对信号的组合使用进行的多重数字分析
WO2012149042A2 (en) 2011-04-25 2012-11-01 Bio-Rad Laboratories, Inc. Methods and compositions for nucleic acid analysis
US9556470B2 (en) 2011-06-02 2017-01-31 Raindance Technologies, Inc. Enzyme quantification
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
EP2737089B1 (en) 2011-07-29 2017-09-06 Bio-rad Laboratories, Inc. Library characterization by digital assay
WO2013020775A2 (en) * 2011-08-11 2013-02-14 Nestec S.A. Liquid-cryogen injection cooling devices and methods for using same
KR20130085759A (ko) * 2012-01-20 2013-07-30 삼성전자주식회사 스탬프 및 그 제조 방법 및 이를 이용한 임프린트 방법
US9322054B2 (en) 2012-02-22 2016-04-26 Lockheed Martin Corporation Microfluidic cartridge
WO2013155531A2 (en) 2012-04-13 2013-10-17 Bio-Rad Laboratories, Inc. Sample holder with a well having a wicking promoter
US10273541B2 (en) 2012-08-14 2019-04-30 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9701998B2 (en) 2012-12-14 2017-07-11 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10323279B2 (en) 2012-08-14 2019-06-18 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9951386B2 (en) 2014-06-26 2018-04-24 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10221442B2 (en) 2012-08-14 2019-03-05 10X Genomics, Inc. Compositions and methods for sample processing
US10752949B2 (en) 2012-08-14 2020-08-25 10X Genomics, Inc. Methods and systems for processing polynucleotides
US11591637B2 (en) 2012-08-14 2023-02-28 10X Genomics, Inc. Compositions and methods for sample processing
CN113528634A (zh) 2012-08-14 2021-10-22 10X基因组学有限公司 微胶囊组合物及方法
US10584381B2 (en) 2012-08-14 2020-03-10 10X Genomics, Inc. Methods and systems for processing polynucleotides
ITTO20120773A1 (it) * 2012-09-06 2012-12-06 Start Up S R L Cartuccia perfezionata per dosatore automatico portatile e dosatore automatico portatile dotato di tali cartucce.
US9990464B1 (en) 2012-10-09 2018-06-05 Pall Corporation Label-free biomolecular interaction analysis using a rapid analyte dispersion injection method
EP3567116A1 (en) 2012-12-14 2019-11-13 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10533221B2 (en) 2012-12-14 2020-01-14 10X Genomics, Inc. Methods and systems for processing polynucleotides
EP2935908B1 (en) 2012-12-21 2019-08-14 PerkinElmer Health Sciences, Inc. Fluidic circuits and related manufacturing methods
CN104919035B (zh) 2012-12-21 2017-08-11 精密公司 便携式荧光检测系统和微测定盒
JP6935167B2 (ja) 2012-12-21 2021-09-15 ペルキネルマー ヘルス サイエンシーズ， インコーポレイテッド マイクロ流体使用のための低弾性フィルム
CN105050720A (zh) 2013-01-22 2015-11-11 华盛顿大学商业化中心 顺序递送流体体积和相关的设备、系统和方法
KR102190198B1 (ko) 2013-02-08 2020-12-14 10엑스 제노믹스, 인크. 폴리뉴클레오티드 바코드 생성
US20160296945A1 (en) 2013-03-15 2016-10-13 Ancera, Inc. Systems and methods for active particle separation
US10793820B2 (en) * 2013-04-30 2020-10-06 Lawrence Livermore National Security, Llc Miniaturized, automated in-vitro tissue bioreactor
WO2014182844A1 (en) 2013-05-07 2014-11-13 Micronics, Inc. Microfluidic devices and methods for performing serum separation and blood cross-matching
EP2994543B1 (en) 2013-05-07 2018-08-15 Micronics, Inc. Device for preparation and analysis of nucleic acids
US10190153B2 (en) 2013-05-07 2019-01-29 Micronics, Inc. Methods for preparation of nucleic acid-containing samples using clay minerals and alkaline solutions
US11901041B2 (en) 2013-10-04 2024-02-13 Bio-Rad Laboratories, Inc. Digital analysis of nucleic acid modification
JP6240327B2 (ja) * 2013-11-27 2017-11-29 ゼネラル・エレクトリック・カンパニイ 流体ロックとパージ装置とを有する燃料ノズル
US9944977B2 (en) 2013-12-12 2018-04-17 Raindance Technologies, Inc. Distinguishing rare variations in a nucleic acid sequence from a sample
WO2015103367A1 (en) 2013-12-31 2015-07-09 Raindance Technologies, Inc. System and method for detection of rna species
WO2015157567A1 (en) 2014-04-10 2015-10-15 10X Genomics, Inc. Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same
CN105013363A (zh) * 2014-04-30 2015-11-04 郑州天一萃取科技有限公司 液液螺旋混合器
CN106660058B (zh) * 2014-05-16 2019-09-17 克维拉公司 用于执行自动化离心分离的设备、系统和方法
EP3161160B1 (en) 2014-06-26 2021-10-13 10X Genomics, Inc. Methods of analyzing nucleic acids from individual cells or cell populations
JP2017532042A (ja) 2014-10-29 2017-11-02 １０エックス ゲノミクス，インコーポレイテッド 標的化核酸配列決定のための方法及び組成物
US9975122B2 (en) 2014-11-05 2018-05-22 10X Genomics, Inc. Instrument systems for integrated sample processing
SG11201705615UA (en) 2015-01-12 2017-08-30 10X Genomics Inc Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same
EP4286516A3 (en) 2015-02-24 2024-03-06 10X Genomics, Inc. Partition processing methods and systems
WO2016138148A1 (en) 2015-02-24 2016-09-01 10X Genomics, Inc. Methods for targeted nucleic acid sequence coverage
US9610578B2 (en) * 2015-05-20 2017-04-04 Massachusetts Institute Of Technology Methods and apparatus for microfluidic perfusion
US11285490B2 (en) 2015-06-26 2022-03-29 Ancera, Llc Background defocusing and clearing in ferrofluid-based capture assays
US9733239B2 (en) 2015-07-24 2017-08-15 HJ Science & Technology, Inc. Reconfigurable microfluidic systems: scalable, multiplexed immunoassays
US9956557B2 (en) 2015-07-24 2018-05-01 HJ Science & Technology, Inc. Reconfigurable microfluidic systems: microwell plate interface
US9956558B2 (en) 2015-07-24 2018-05-01 HJ Science & Technology, Inc. Reconfigurable microfluidic systems: homogeneous assays
US10647981B1 (en) 2015-09-08 2020-05-12 Bio-Rad Laboratories, Inc. Nucleic acid library generation methods and compositions
CN106607109A (zh) * 2015-10-26 2017-05-03 宁波大学 涉及廉价疏水基片的常见肿瘤标志物筛查用芯片装置
EP3380239B1 (en) * 2015-11-25 2023-08-23 Spectradyne, LLC Systems and devices for microfluidic instrumentation
CN108431232B (zh) 2015-12-04 2022-10-14 10X 基因组学有限公司 用于核酸分析的方法和组合物
DE102016103781A1 (de) * 2016-03-03 2017-09-07 Cvp Clean Value Plastics Gmbh Vorrichtung und Verfahren zum gemeinsamen Eintragen von Kunststoffteilchen und einer Flüssigkeit in eine Reinigungsvorrichtung
WO2017197338A1 (en) 2016-05-13 2017-11-16 10X Genomics, Inc. Microfluidic systems and methods of use
US11422107B2 (en) 2016-12-07 2022-08-23 Radiometer Medical Aps System and method for estimating a temperature of a liquid sample
US10011872B1 (en) 2016-12-22 2018-07-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10815525B2 (en) 2016-12-22 2020-10-27 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10550429B2 (en) 2016-12-22 2020-02-04 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10258741B2 (en) 2016-12-28 2019-04-16 Cequr Sa Microfluidic flow restrictor and system
CN117512066A (zh) 2017-01-30 2024-02-06 10X基因组学有限公司 用于基于微滴的单细胞条形编码的方法和系统
CN110537087A (zh) * 2017-02-19 2019-12-03 工业研究与发展基金会有限公司 药敏试验试剂盒
US11192103B2 (en) * 2017-05-04 2021-12-07 University Of Utah Research Foundation Micro-fluidic device for rapid PCR
CN109526228B (zh) 2017-05-26 2022-11-25 10X基因组学有限公司 转座酶可接近性染色质的单细胞分析
US10400235B2 (en) 2017-05-26 2019-09-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
EP3625361A1 (en) 2017-11-15 2020-03-25 10X Genomics, Inc. Functionalized gel beads
US10829815B2 (en) 2017-11-17 2020-11-10 10X Genomics, Inc. Methods and systems for associating physical and genetic properties of biological particles
WO2019195166A1 (en) 2018-04-06 2019-10-10 10X Genomics, Inc. Systems and methods for quality control in single cell processing
CA3098905A1 (en) 2018-04-30 2019-11-07 Protein Fluidics, Inc. Valveless fluidic switching flowchip and uses thereof
US11032964B2 (en) 2018-06-27 2021-06-15 Cnh Industrial Canada, Ltd. Flow splitting control valve for secondary header
CN109107624A (zh) * 2018-10-16 2019-01-01 长春技特生物技术有限公司 一种全封闭微流控芯片和乳液微滴制备系统
CN109550527A (zh) * 2018-12-06 2019-04-02 中南大学 有多数量级浓度稀释功能的微流控芯片装置及其应用方法
AU2020214425A1 (en) * 2019-01-31 2021-08-19 Modernatx, Inc. Vortex mixers and associated methods, systems, and apparatuses thereof
JP7430798B2 (ja) * 2019-12-19 2024-02-13 ラジオメーター・メディカル・アー・ペー・エス 多孔質膜センサ組立体
CN111773993B (zh) * 2020-07-01 2021-10-19 西安交通大学 一种外场作用下的逆流喷射冷热流体混合器

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3398689A (en) * 1966-01-05 1968-08-27 Instrumentation Specialties Co Apparatus providing a constant-rate two-component flow stream
US3935971A (en) * 1973-05-30 1976-02-03 Consiglio Nazionale Delle Ricerche Double pump device for mixing two or more liquids with variable relative ratios and concentrations
US4239623A (en) * 1979-02-10 1980-12-16 Hewlett-Packard Company Apparatus for producing gradient elution in a liquid chromatographic system
GB2162437A (en) * 1984-07-05 1986-02-05 Magnetopulse Ltd Improvements in and relating to liquid chromatography
US5253981A (en) * 1992-03-05 1993-10-19 Frank Ji-Ann Fu Yang Multichannel pump apparatus with microflow rate capability

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3795451A (en) * 1973-04-24 1974-03-05 Atomic Energy Commission Rotor for fast analyzer of rotary cuvette type
US3873217A (en) * 1973-07-24 1975-03-25 Atomic Energy Commission Simplified rotor for fast analyzer of rotary cuvette type
US4131426A (en) * 1977-08-24 1978-12-26 Baxter Travenol Laboratories, Inc. Tip wiper apparatus and method
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4812392A (en) * 1984-12-27 1989-03-14 Sumitomo Electric Industries, Ltd. Method and apparatus for incubating cells
US5333675C1 (en) * 1986-02-25 2001-05-01 Perkin Elmer Corp Apparatus and method for performing automated amplification of nucleic acid sequences and assays using heating and cooling steps
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4827780A (en) * 1986-04-17 1989-05-09 Helena Laboratories Corporation Automatic pipetting apparatus
US4753535A (en) * 1987-03-16 1988-06-28 Komax Systems, Inc. Motionless mixer
US5252294A (en) * 1988-06-01 1993-10-12 Messerschmitt-Bolkow-Blohm Gmbh Micromechanical structure
US5270183A (en) * 1991-02-08 1993-12-14 Beckman Research Institute Of The City Of Hope Device and method for the automated cycling of solutions between two or more temperatures
JPH05509170A (ja) * 1991-06-18 1993-12-16 クールター　コーポレイション 取り外し交換可能な吸引ニードルカートリッジ組立体
US5498392A (en) * 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
US5486335A (en) * 1992-05-01 1996-01-23 Trustees Of The University Of Pennsylvania Analysis based on flow restriction
DE69429038T2 (de) * 1993-07-28 2002-03-21 Pe Corporation (Ny), Norwalk Vorrichtung und Verfahren zur Nukleinsäurevervielfältigung
JP2948069B2 (ja) * 1993-09-20 1999-09-13 株式会社日立製作所 化学分析装置
DE4435107C1 (de) * 1994-09-30 1996-04-04 Biometra Biomedizinische Analy Miniaturisierter Fluß-Thermocycler
US5640995A (en) * 1995-03-14 1997-06-24 Baxter International Inc. Electrofluidic standard module and custom circuit board assembly
US5716852A (en) * 1996-03-29 1998-02-10 University Of Washington Microfabricated diffusion-based chemical sensor
US6454945B1 (en) * 1995-06-16 2002-09-24 University Of Washington Microfabricated devices and methods
DE69628016T2 (de) * 1995-06-16 2004-04-01 University Of Washington, Seattle Miniaturisierte differentielle extraktionsvorrichtung und verfahren
US5856174A (en) * 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
US6130098A (en) 1995-09-15 2000-10-10 The Regents Of The University Of Michigan Moving microdroplets
US6057149A (en) * 1995-09-15 2000-05-02 The University Of Michigan Microscale devices and reactions in microscale devices
US20010055812A1 (en) * 1995-12-05 2001-12-27 Alec Mian Devices and method for using centripetal acceleration to drive fluid movement in a microfluidics system with on-board informatics
US6114122A (en) * 1996-03-26 2000-09-05 Affymetrix, Inc. Fluidics station with a mounting system and method of using
US5948684A (en) * 1997-03-31 1999-09-07 University Of Washington Simultaneous analyte determination and reference balancing in reference T-sensor devices
US5860182A (en) * 1996-04-08 1999-01-19 Sareyani; Peter Hand-held windshield wiper blade cleaner
US5964239A (en) * 1996-05-23 1999-10-12 Hewlett-Packard Company Housing assembly for micromachined fluid handling structure
US5939291A (en) * 1996-06-14 1999-08-17 Sarnoff Corporation Microfluidic method for nucleic acid amplification
US5863801A (en) * 1996-06-14 1999-01-26 Sarnoff Corporation Automated nucleic acid isolation
US5804436A (en) * 1996-08-02 1998-09-08 Axiom Biotechnologies, Inc. Apparatus and method for real-time measurement of cellular response
US5984519A (en) * 1996-12-26 1999-11-16 Genus Corporation Fine particle producing devices
US6117634A (en) * 1997-03-05 2000-09-12 The Reagents Of The University Of Michigan Nucleic acid sequencing and mapping
US6126904A (en) * 1997-03-07 2000-10-03 Argonaut Technologies, Inc. Apparatus and methods for the preparation of chemical compounds
DE19717085C2 (de) * 1997-04-23 1999-06-17 Bruker Daltonik Gmbh Verfahren und Geräte für extrem schnelle DNA-Vervielfachung durch Polymerase-Kettenreaktionen (PCR)
US6090251A (en) * 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
US5974867A (en) * 1997-06-13 1999-11-02 University Of Washington Method for determining concentration of a laminar sample stream
US5916776A (en) * 1997-08-27 1999-06-29 Sarnoff Corporation Amplification method for a polynucleotide
US5965410A (en) * 1997-09-02 1999-10-12 Caliper Technologies Corp. Electrical current for controlling fluid parameters in microchannels
US6102068A (en) * 1997-09-23 2000-08-15 Hewlett-Packard Company Selector valve assembly
US6007775A (en) * 1997-09-26 1999-12-28 University Of Washington Multiple analyte diffusion based chemical sensor
US5887977A (en) * 1997-09-30 1999-03-30 Uniflows Co., Ltd. Stationary in-line mixer
US6187530B1 (en) * 1997-10-03 2001-02-13 Monterey Bay Aquarium Research Institute Aquatic autosampler device
US6210882B1 (en) * 1998-01-29 2001-04-03 Mayo Foundation For Medical Education And Reseach Rapid thermocycling for sample analysis
AU763497B2 (en) * 1998-10-13 2003-07-24 Biomicro Systems, Inc. Fluid circuit components based upon passive fluid dynamics
EP1121199B1 (fr) * 1998-10-16 2003-12-17 Commissariat A L'energie Atomique Dispositif d'analyse chimique et/ou biochimique avec un support d'analyse
US6193471B1 (en) 1999-06-30 2001-02-27 Perseptive Biosystems, Inc. Pneumatic control of formation and transport of small volume liquid samples
US6123107A (en) * 1999-07-09 2000-09-26 Redwood Microsystems, Inc. Apparatus and method for mounting micromechanical fluid control components
FR2796863B1 (fr) * 1999-07-28 2001-09-07 Commissariat Energie Atomique Procede et dispositif permettant de realiser en flux continu un protocole de traitement thermique sur une substance
US6772500B2 (en) 2001-10-25 2004-08-10 Allfast Fastening Systems, Inc. Method of forming holes for permanent fasteners

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3398689A (en) * 1966-01-05 1968-08-27 Instrumentation Specialties Co Apparatus providing a constant-rate two-component flow stream
US3935971A (en) * 1973-05-30 1976-02-03 Consiglio Nazionale Delle Ricerche Double pump device for mixing two or more liquids with variable relative ratios and concentrations
US4239623A (en) * 1979-02-10 1980-12-16 Hewlett-Packard Company Apparatus for producing gradient elution in a liquid chromatographic system
GB2162437A (en) * 1984-07-05 1986-02-05 Magnetopulse Ltd Improvements in and relating to liquid chromatography
US5253981A (en) * 1992-03-05 1993-10-19 Frank Ji-Ann Fu Yang Multichannel pump apparatus with microflow rate capability

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111132765A (zh) * 2017-09-19 2020-05-08 高保真生物技术有限公司 微流体系统中的颗粒分选
CN111132765B (zh) * 2017-09-19 2022-05-13 高保真生物技术有限公司 微流体系统中的颗粒分选

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